Device to monitor retinal ischemia

ABSTRACT

A battery powered, hand held device to determine of there is significant retinal ischemia in the eye of a patient. The device detects the consequences of impaired blood flow in the eye of the patient and has a light source for emitting a light and a diffuser or diffuse spheroidal reflector that redirects the light from the light source toward the patient&#39;s eye. A set of electrodes contact the patients skin proximate to the eye and receives an electrical signal representing the eye&#39;s electrical response to the light stimulus. A microcontroller interprets the electrical signal sensed by the electrodes by using an algorithm to determine the degree of retinal ischemia of the patient. In one embodiment, there is a control that establishes the intensity of the light stimulus by measuring and using the area of the pupil.

FIELD OF THE INVENTION

The present invention relates to a device for monitoring retinalischemia and, more particularly, to a hand held device that can easilydetermine if the eye of a patient is receiving sufficient blood flow.

BACKGROUND OF THE INVENTION

Diabetic retinopathy is a disease caused by progressively impaired bloodflow to the retina of the eye. This impaired blood flow eventually leadsto oxygen deprivation, or ischemia of the retina. Over time, theischemia worsens and the retina begins to secrete hormones to producenew blood vessels. These blood vessels are very fragile and grow ininappropriate parts of the eye. They can rupture leading to blindness.Other conditions caused by worsening ischemia in the diabetic eyeinclude macular edema, where the central part of the eye responsible forgood vision develops a fluid bubble leading to poor central vision.

The progress of the disease can today be detected by an ophthalmologist,and when the disease is severe enough, it can be treated by burning theretina repeatedly with a laser (panretinal photocoagulation) which stopsthe secretion of angiogenic hormones (or inhibits their action). Thereare also drug therapy interventions available and under development thatmay delay the onset of inappropriate blood vessel development.

Accordingly, early detection of diabetic retinopathy would allowintervention at an earlier stage of the disease allowing better qualityof life for diabetics whose vision could be preserved for a longerperiod of time. The American Academy of Ophthalmology recommends thatdiabetics that have had the condition for more than ten years get an eyeexamination annually. Despite the availability of diagnosis andtreatment, diabetic retinopathy is the leading cause of blindness inworking-age Americans, and is one of the leading causes of blindnessworldwide.

At the present, ophthalmologists rely on two primary diagnostic testsfor assessment of diabetic retinopathy.

-   -   1. Fundus photography is the practice of taking careful        photographs of the back of the eye and grading them for the        presence of certain characteristics. The photographs are        typically taken by a highly trained technician using a        specialized camera called a fundus camera. The grading of the        photographs is performed either by an ophthalmologist or by        specially trained “graders”.    -   2. Fluorescein angiography involves injecting a fluorescent dye        into the patient's vein and photographing the time course of the        dye passing through the eye using a specialized camera system.        This technique allows the assessment of blood flow across the        surface of the eye, and allows an assessment of leakage from the        blood vessels. Fluorescein angiography is performed by        ophthalmologists or certified technicians and the interpretation        of the photographs is performed either by an ophthalmologist or        by specially trained “graders”.

Diabetic retinopathy is not the only disease to cause damage to the eyethrough the mechanism of retinal ischemia. Less prevalent diseases,including central retinal vein occlusion (CRVO), central retinal arteryocclusion (CRAO) and sickle cell anemia may also induce retinal ischemialeading to the growth of inappropriate new blood vessels in the eye.

It has been known for some time that features of the clinicalelectroretinogram (ERG) are strongly correlated with retinal ischemiaand with the extent and severity of diabetic retinopathy. There are manyreports in the academic literature describing the relationship betweenfeatures of the ERG and severity of several types of retinal ischemia.Some of the articles include the following: Bresnick, G, Korth, K, Groo,A. and Palta, M. Archives of Ophthalmology 102: 1307-11 (1984)Electroretinographic oscillatory potentials predict progression ofdiabetic retinopathy; Bresnick, G. and Palta, M, Archives ofOphthalmology 105:60-664 (1987) Temporal aspects of theelectroretinogram in diabetic retinopathy, and Bresnick, G and Palta, M,Archives of Ophthalmology 105: 929-33 (1987) Oscillatory potentialamplitudes, Relation to severity of diabetic retinopathy.

Normally the ERG is recorded using a large instrument in a darkened roomwith electrodes placed directly onto the eye. Dilating drops are used toenlarge the pupil and anesthetic drops are used to numb the eye beforeplacing the electrodes onto the eye. The waveforms are collected by askilled technician and are usually interpreted by an ophthalmologist orPhD expert in visual electrophysiology. The aforedescribed disadvantagesof the ERG have prevented its widespread use in assessing retinalischemia.

As can therefore be seen, the present systems and methods of detectingretinal ischemia are by fundus photography, fluorescein angiography orby using a conventional ERG system. All of such methods requireexpensive equipment and facilities as well as highly trained personnelto operate and interpret the results.

Accordingly, it would, therefore, be desirable to have an inexpensive,hand held device that would be easy to operate, require little or notraining to operate and interpret the results. It would be furtheradvantageous to have such a device that could be used by generalpractice physicians to assess the health of diabetic eyes and thussignificantly improve the number of diabetic eyes that are screened forretinopathy.

BRIEF SUMMARY OF THE INVENTION

Accordingly, the present invention relates to a compact, handheldelectroretinographic monitoring device to assess retinal ischemia in theeyes of patients with diabetes or other ischemic eye diseases.

The present monitoring device can be manually placed in contact with theskin in proximity to the subject's eye and has a light source that emitsa flash of light into the eye. The light is provided by a high intensitylight emitting diode and that light is directed toward the eye by adiffuse spheroidal reflector to provide a uniform light into the eye. Areturn signal is received from the eye in response to the light stimulusand is detected by electrodes that contact the skin proximate to theeye. In an exemplary embodiment, there are three electrodes; a sideelectrode and two other electrodes oriented vertically with respect tothe side electrode. The received signal is detected by the sideelectrode and one of the other electrodes.

In an exemplary embodiment, the electrodes are located in an electrodeholder that is rotatably mounted to a hand held portion of themonitoring device and the electrode holder can be rotated with respectto the hand held portion in order to accommodate the difference in theanatomy of both the left and the right eyes of the subject. There canalso be a system to determine which eye is being tested by measuring theimpedance between the side electrode and each of the other electrodes orby determining the rotational orientation of the electrode holder withrespect to the hand held portion.

There is an electrical circuit that controls the light directed towardthe eye and measures the electrical signal the eye produces in responseto the light. The time span between the flash of light and the time ofthe peak of the return signal is indicative of the degree of retinalischemia of the patient.

The monitoring device is self-contained, that is, there is battery powerprovided, controls located in the hand held device and an electronicreadout for the user. In an embodiment, there is a detector thatdetermines the area of diameter of the pupil of the eye and determinesthe intensity of the light flash in accordance with that area ordiameter. The detector can be a video camera.

As a further feature, the detector includes a source of illumination toilluminate the pupil and which is preferably a source of infraredradiation.

These and other features and advantages of the present invention willbecome more readily apparent during the following detailed descriptiontaken in conjunction with the drawings herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the hand held device of the presentinvention;

FIG. 2 is a perspective view of the electrode holder which is part ofthe hand held device of FIG. 1; and

FIG. 3 is schematic view of the present invention; and

FIG. 4 is a graph showing light intensities of the background light andstimulus light used with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to FIG. 1, there is shown a hand held retinal ischemiamonitoring device 10 of the present invention. As can be seen, themonitoring device 10 comprises a hand held portion 12 with an electrodeholder 14 at its forward end that has electrodes (not shown in FIG. 1)that are adapted to be placed in contact with the skin of the patientproximate to either eye of the patient when the monitoring device 10 isin its operative position. As will be seen, the electrode holder 14 ispreferably rotatably mounted to the hand held portion 12. The monitoringdevice 10 can have a battery compartment 16 to house the batteries topower its operation. In addition, there is a readout 18, as well asvarious controls 20, the use of which will be later explained.

Turning now to FIG. 2, there is shown a perspective view of theelectrode holder 14 of the present device. In the exemplary embodiment,the electrode holder 14 has a centrally located opening 22 and there arethree electrodes; a side electrode 32 and two other electrodes 34, 36that are located vertically away from the side electrode 32, andgenerally equidistant from the side electrode 32. The spacing of theelectrodes 32, 34 and 36 is designed such that, when the hand heldmonitoring device 10 is placed against the skin of the patient proximateto the eye, the side electrode 32 is oriented at the side of the eye andone of the other two electrodes 34, 36 is in contact with the skin nextto the lower lid of the eye. The remaining electrode is not touching thepatient. Determination of which electrodes are in contact with thepatient is made by measuring the impedance of the electrode pairs andallows the system to automatically establish the eye being tested.

The electrode holder 14 can be rotated 180 degrees with respect to thehand held portion 12 to adjust the orientation of the electrodes 32, 34and 36 for left and right eyes and that rotation can also be sensed inorder to determine which eye is being tested.

In the embodiment illustrated, the electrodes are combined as integralcomponents of the hand held device 10, however, as an alternativeembodiment, the electrodes can be disposable so that they are intendedfor one patient use and thus are readily attachable and detachable fromthe hand held portion 12 of the hand held monitoring device 10. As such,the only part of the hand held monitoring device 10 that actuallycontacts the patient would not need to be disinfected after eachpatient. With that embodiment, the electrodes can be embedded in adisposable plastic sheet so that a new electrode set is used for eachtest, thereby ensuring maximum protection against any infection passingfrom patient to patient.

While three electrodes 32, 34 and 36 are illustrated in FIG. 2, therecan be a lesser number of electrodes that can be used to stilleffectively carry out the present invention. As will later be seen, theuse of three electrodes has other advantages that are gained in the useof the hand held monitoring device 10.

Turning now to FIG. 3, taken along with FIG. 1, there is shown aschematic view of the present invention to illustrate the componentsthat are contained within the hand held monitoring device 10 of FIG. 1.A light source 38 is used to provide a light stimulus to the eye and thelight source 38 can be a light emitting diode, (LED) that is compact andtherefore suitable for a portable device as opposed to the prior artxenon flashtube or array of LED's. The current high brightness LED'shave sufficient brightness for carrying out the present invention withan efficient diffuser, however, it may be that for some applications aplurality of LEDs may be used to make up the light source 38.

The light source is 38 controlled by a microcontroller 40 that, as willbe seen, provides the overall control of the hand held monitoring device10 but is sufficiently small so as to readily fit into the hand heldmonitoring device 10. The light source 38 is positioned so as toprotrude inwardly of a diffuse spheroidal reflector 42 so that the lightfrom the light source is directed uniformly toward the eye 44 from alldirections. In the illustrated embodiment, the diffuse spheroidalreflector 42 is spheroidal in configuration with the interior surfacecoated white to enhance the reflectivity. The use of the diffusespheroidal reflector 42 provides an even illumination to most of theretina of the eye 44.

As stated, the control of the light source 38 is by means of themicrocontroller 40 which not only controls the timing of the firing ofthe LED, but also the intensity thereof. The control of the intensity ofthe light source 38 will be later explained. As to the timing, the LEDprovides a series of brief flashes of light spaced about every 30milliseconds, however, other stimulus waveforms or stimulus frequenciescan also be utilized.

In a preferred embodiment, the intensity of the LED or light source 38is also modulated to produce a constant background illumination. Thatbackground illumination allows the eye 44 to be brought to a known stateof light adaptation, which is important for a consistent response aswill be later be understood.

Turning briefly, therefore to FIG. 4, there is a graph plotting time vs.light intensity illustrating the light intensity of the backgroundillumination, identified as A as well as the intensity of the briefflashes of light identified as B. As can be seen, the backgroundillumination intensity is established and maintained whereas the briefflashes of light are of a high intensity and short duration.

Returning to FIG. 3, as previously explained, the light stimulus by thelight source 38 gives rise to an electrical signal from the eye 44 thatis sensed by the electrodes 32, 34 for example (it could be electrodes32, 36) contacting the skin of the patient proximate to the eye 44 andthe electrical signal is communicated by wires 48 to an amplifier andA/D converter shown as block 50. The amplifier is preferably abiomedical amplifier using 24 bit analog to digital converters thateliminates gain adjustment and the prolonged recovery from saturation ofconventional amplifiers.

Typically, conventional amplifiers have required some oversight by atechnician during testing to assure that the gain setting was correctlymatched to the input range of the analog to digital converter. Further,such conventional amplifiers could saturate (fail to respond to theinput signal) and might take tens of seconds to recover the ability torespond to a signal. The saturation is difficult to distinguish from alack of response from the patient making reliable automation of signalacquisition difficult.

To avoid the problems, in a preferred embodiment, the system used a lowgain differential amplifier (no more than 32×) and a high resolution(typically 24 bit) differential analog to digital converter to acquirethe signal from the eye 44 by means of the skin electrodes 32, 34. Thus,the amplifier has a very high tolerance for noise and offsets, whileproducing highly faithful reproduction of the input waveform. Theamplifier and A/D converter of block 50 are also immune to prolongedsaturation caused by interfering signals. Input impedance of the systemis very high (>10 MΩ) so that the relatively high impedance of theelectrodes 32, 34 contacting the skin does not affect the results. Theoutput of the analog to digital converter in block 50 is connected tothe microcontroller 40, which analyzes the data.

A further feature of the present hand held monitoring device 10 is thatthere is a system to determine which eye 44 is being tested by thedevice i.e the right eye or the left eye. Returning briefly to FIG. 2,in that exemplary embodiment, there are three electrodes 32, 34 and 36that are formed in the configuration of a triangle with one electrode 32along the side of the eye 44 with the other two electrodes 34, 36located vertically offset with respect to the side electrode 32. Thusthe system to determine which eye is being tested provides a low currentsource between pairs of electrodes to measure the electrode impedance.The current is used to determine the particular eye being tested and isswitched off during the testing itself and only the two electrodesdetermined to be touching the skin are used to carry out the testingprocedure. Accordingly, the testing will be carried out using the sideelectrode 32 and either one of the other two electrodes 34 or 36.

As a further feature of the present invention, and which may beoptional, there is a system to establish the intensity of the lightsource 38 based upon the area of the pupil of the eye 44 so that thelight stimulus to the retina will be constant among the various patientswithout the need for dilating drops to be placed in the eye to widen thepupil. Accordingly the system comprises a video camera 52 that ispositioned so as to view the pupil of the eye 44 and measure the area ofthe pupil. The video camera 52 can be a small, relatively low resolution(e.g. 320-240 pixel) device having an illumination source to illuminatethe pupil for the video camera 52.

The illumination source for the pupil measurement system is preferablyone or more infrared LED's that are located nearly coaxial with the lensof the video camera 52 to so that the reflected light from the interiorof the eye 44 creates a highly visible pupil to the video camera 52.With the use of infrared light radiation the light is not visible to theeye but does provide sufficient illumination for the video camera 52. Assuch, the area of the pupil can be readily determined through a simplethresholding and pixel counting algorithm. There are several system formeasuring the pupil area that are published in the art and one is shownand described in Investigative Ophthalmology and Visual Science,17:702-705 (1978) by Salidin, J J and entitled Television Pupillometryvia digital time processing.

In any event, the area of the pupil can be determined by themicrocontroller 40 so that the intensity of the light source 38 isestablished based on that pupil area such that the light stimulus isbasically the same for each patient and for successive tests with samepatient. The system can also be used to determine if the eye is shut,for example, in the event of a blink, and eliminate that part of thesignal from the analysis.

The analysis of the data from the electrical signals sensed by theelectrodes 32, 34 is, as described, carried out by the microcontroller40. The algorithms for specifically assessing retinal ischemia in apatient have been published. See, for example, Applied Optics30:2106-2112 (1991) by Severns, M L, Johnson, M A and Merritt, S AAutomated estimate of implicit time and amplitude of the flickerelectroretinogram and 1991 Technical Digest Series, Washington, D.C;Optical Society of America, pp. 10-13 (1991) by Severns, M L andJohnson, M A Automated implicit time and amplitude determination for the30 Hz flicker electroretinogram: performance prediction ofneovascularization central retinal vein occlusion.

In an exemplary embodiment, the signals from the skin electrodes 32, 34are analyzed for the amount of noise present to determine if accurateand clinically meaningful measurements can be made. If the signal tonoise ratio is marginal, additional data can be collected to improve theestimate. Next, a sine wave is fit to the data to determine the amountof elapsed time between the actuation of the stimulus and the maximalresponse of the eye. This measurement has been shown to be a highlysensitive measure of the extent of ischemia in the eye. See the AppliedOptics publication previously cited.

As further components of the present hand held monitoring device 10,(FIG. 1) there are controls 20 that can be used to initiate each testand to enter customized settings. In addition, the readout 18 provides avisual readout to the user of the results of each test, that is, thereadout 18 provides a visual readout to the user that is related to theamount of retinal ischemia of the eye.

Accordingly, the operation of the hand held device 10 can now besummarized, using FIGS. 1-4. The electrode holder 14 is adjusted for theeye to be tested by rotating it to the appropriate orientation. The handheld device 10 is held against the patient proximate to the eye of thepatient such that at least two of the skin electrodes 32 and 34 or 32and 36 contact the skin of the patient. The hand held monitoring device10 is initialized by pressing a button on the device by means of thecontrols 20. The battery power is thus engaged to power themicrocontroller 40 that energizes the light source 38 to provide acontinual adapting or background light of a predetermined, relativelylow intensity for a period of about 1 minute.

Next, the microcontroller 40 determines which eye is being tested bydetermining the impedance between the side electrode and each of theother electrodes. Once the identification of the eye has beendetermined, the impedance measurement is discontinued. Alternatively,the eye being tested can be determined by sensing the rotationalorientation of the electrode holder 14 relative to the hand held portion12

The microcontroller 40 then commences the flashing of the light source38 at about 30 Hz to stimulate the retina. At the same time, the videocamera 52 measures the area of the pupil and the microcontroller 40adjusts the intensity of the light source 38 in accordance with thatarea. As indicated, that feature may not be used with every applicationof the device 10. The microcontroller then receives the electricalsignal produced by the eye from the skin electrodes 32, 34 and theelectrical signal is fed into the microcontroller 40 for processing todetermine, using known algorithms, the resulting electroretinogram andpresent the elapsed delay time between the light stimulus and the peakof the received electrical signal (or interpret the electroretinogram ofthe skin electrodes 32, 34) and an estimate of the reliability of themeasurement on the readout 18.

In an alternative embodiment, the waveform data can be displayed on thereadout 18 or downloaded to a reading unit for viewing by the physician.The data and results also may be printed out to be entered into thepatient record as hard copy or electronically.

Those skilled in the art will readily recognize numerous adaptations andmodifications which can be made to the hand held retinal ischemicmonitoring device of the present invention which will result in animproved device an method of using the same, yet all of which will fallwithin the scope and spirit of the present invention as defined in thefollowing claims. Accordingly, the invention is to be limited only bythe following claims and their equivalents.

1. A hand held device to detect the effects of impaired blood flow inthe eye of a subject, the device comprising: a light source for emittinga light, a light diffusing means adapted to receive the light from thelight source and to redirect the light toward the eye of a subject,wherein the light diffusing means redirects the light to provide asubstantially even illumination to the retina of the eye; means toprovide the retina with substantially constant illumination from thelight, regardless of the size of the pupil of the eye; at least oneelectrode adapted to contact the subject at a location proximate to theeye, the at least one electrode receiving an electrical signal from theeye of the subject responding to the stimulation by the light directedtoward the eye, and an electronic circuit to control the light directedtoward the eye of the subject and to measure the electrical signalreceived by the at least one electrode to determine whether blood flowis impaired within the eye of a subject.
 2. The hand-held device ofclaim 1 wherein the light diffusing means is a diffuse spheroidalreflector.
 3. The hand-held device of claim 1 wherein the light sourceis a light emitting diode.
 4. The hand-held device of claim 1 whereinthe electronic circuit measures the elapsed time between the time thelight is directed toward the eye and the time the peak electrical signalis detected by the at least one electrode.
 5. The hand-held device ofclaim 1 wherein the device includes batteries to power the light sourceand the electronic circuit.
 6. The hand-held device of claim 1 whereinthe means to provide the retina with substantially constant illuminationincludes a detector to determine the diameter or area of the pupil of aneye.
 7. The hand-held device of claim 6 wherein the detector is a videocamera.
 8. The hand held device of claim 7 wherein the video cameraincludes an illumination device to illuminate the pupil for viewing bythe video camera.
 9. The hand held device of claim 8 wherein theillumination device is a source of infrared radiation.
 10. The hand-helddevice of claim 6 wherein the means to provide the retina withsubstantially constant illumination further includes an electroniccircuitry to establish the intensity of the light in accordance with thediameter or area of the pupil determined by the detector.
 11. Thehand-held device of claim 1 wherein at least one electrode comprisesthree electrodes.
 12. The hand-held device of claim 11 wherein thedevice comprises a hand held portion and an electrode holder that isrotatably mounted to the hand held portion.
 13. The hand-held device ofclaim 12 further including an electronic circuit to interrogate theelectrodes or to sense their position relative to the hand held portionto determine whether the device is being positioned proximate to theright eye or the left eye of a subject.
 14. The hand-held device ofclaim 11 wherein the electrical signal is received by one electrodepositioned at the side of an eye and one of the other electrodes.
 15. Amethod of determining whether the blood flow within the eye of a subjectis impaired, the method comprising the steps of: providing a hand helddevice having a light source, a light diffuse reflector and at least oneelectrode, positioning the device such that the at least one electrodecontacts the skin of the subject proximate the eye, activating the lightsource to direct light towards the eye of a subject, wherein the lightautomatically provides substantially even and constant illumination tothe retina of the eye regardless of the size of the pupil of the eye,detecting an electrical signal by the at least one electrode responsiveto the stimulation of the eye by the light, and determining whetherblood flow within the eye is impaired by using a signal indicative ofactivating the light source and the electrical signal detected by the atleast one electrode.
 16. The method of claim 15 wherein the step ofproviding a hand held device comprises providing a hand held devicehaving a light source comprising a light emitting diode.
 17. The methodof claim 15 wherein the step of providing a hand held device comprisesproviding a hand held device having three electrodes.
 18. The method ofclaim 17 wherein the step of positioning the device comprisespositioning the device such that one electrode contacts the subjectsskin at the side of an eye and another electrode contacts the skin ofthe subject below the eye.
 19. The method of claim 15 wherein the stepof determining if the blood flow is impaired comprises measuring thetime between the activation of the light source and the time theelectrical signal is detected by the at least one electrode reaches itsmaximum value.
 20. The method of claim 15 wherein the step of providinga hand held device comprises providing a hand held device having adiffuse spheroidal reflector.
 21. A system for detecting the retinalischemia of a patient comprising: a hand held device to detect impairedblood flow in the eye of a subject, the device comprising a light sourcefor emitting a light, a reflector or diffuser adapted to receive thelight from the light source and to redirect the light toward the eye ofa subject,wherein the reflector or diffuser redirects the light,providing substantially even illumination to the retina of the eye;means to provide the retina with substantially constant illuminationfrom the light, regardless of the size of the pupil of the eye; at leastone electrode adapted to contact the subject at a location proximate tothe eye, the at least one electrode receiving an electrical signal fromthe subject responding to the stimulation by the light directed towardthe eye of the subject, an amplifier and an analog to digital converterto provide a digitized signal indicative of the electrical signal fromthe subject, and a microcontroller, the microcontroller activating thelight source and adapted to receive the digitized signal from thesubject from the at least one electrode, the microcontroller using theactivation of the light source and the digitized signals to determinethe retinal ischemia of a patient.
 22. The system as defined in claim 21wherein the amplifier is a low gain differential amplifier.
 23. Thesystem as defined in claim 21 wherein the microcontroller controls theintensity of the light source.
 24. The system as defined in claim 23wherein the means to provide the retina with substanially constantillumination includes a system to determine the area of the pupil of aneye and wherein the microcontroller controls the intensity of the lightsource based on the pupil area.
 25. The system as defined in claim 21wherein the light source emits brief light flashes and themicrocontroller controls the frequency of activation of brief flashes ofthe light source.
 26. The system as defined in claim 25 wherein themicrocontroller controls the frequency of the brief flashes to be aboutevery 30 milliseconds.
 27. The system as defined in claim 24 wherein thesystem to determine the area of the pupil comprises a video camerahaving a source of illumination.
 28. The system as defined in claim 27wherein the source of illumination comprises an infrared light source.29. The system as defined in claim 21 wherein the reflector or diffuseris a diffuse spheroidal reflector having a diffuse light reflectingsurface.
 30. The system as defined in claim 21 wherein the light sourceis at least one light emitting diode.
 31. The hand held device of claim1 wherein the means to provide the retina with substantially constantillumination includes an electronic circuit to control the light so asto automatically provide the substantially even and constantillumination to the retina of the eye regardless of the size of thepupil of the eye.
 32. The system of claim 21 wherein the microcontrollercontrols the light source so as to automatically provide thesubstantially even and constant illumination to the retina of the eyeregardless of the size of the pupil of the eye.
 33. A hand held deviceto detect the effects of impaired blood flow in the eye of a subject,the device comprising: a light source for emitting a light, a lightdiffusing means adapted to receive the light from the light source andto redirect the light toward the eye of a subject, wherein the lightdiffusing means redirects the light, providing substantially evenillumination to the retina of the eye; means to provide the retina withsubstantially constant illumination from the light, regardless of thesize of the pupil of the eye; and at least one electrode adapted tocontact the subject at a location proximate to the eye, the at least oneelectrode receiving an electrical signal from the eye of the subjectresponding to the stimulation by the light directed toward the eye,wherein the electrical signal contains information indicating whetherthe eye is deprived of oxygen.
 34. A hand held device to measurediabetic retinopathy in the eye of a subject, the device comprising: alight source for emitting a light, a light diffusing means adapted toreceive the light from the light source and to redirect the light towardthe eye of a subject, wherein the light diffusing means redirects thelight uniformly, providing substantially even illumination to the retinaof the eye; means to provide the retina with substantially constantillumination from the light, regardless of the size of the pupil of theeye; and at least one electrode adapted to contact the subject at alocation proximate to the eye, the at least one electrode receiving anelectrical signal from the eye of the subject responding to thestimulation by the light directed toward the eye, wherein the electricalsignal contains information indicating whether the eye is afflicted withdiabetic retinopathy.
 35. The hand held device of claim 34 furthercomprising a readout that provides a visual readout related to theseverity of the diabetic retinopathy.
 36. The hand held device of claim34 further comprising a microcontroller programmed to analyze theelectrical signal information to determine the severity of diabeticretinopathy in the eye.